Selegiline

Caution is advised when selegiline is taken in combination with other centrally acting medicinal products and substances. The concomitant intake of alcohol should be avoided.

Selegiline should be used with caution in severe kidney dysfunction.

Selegiline should be used with caution in severe liver dysfunction.

The combination of selegiline and oral contraceptives or drugs for hormone replacement therapy, should be avoided, as this combination may increase the bioavailability of selegiline.

In view of the high degree of binding to plasma proteins by selegiline particular attention must be given to patients who are being treated with medicines with a narrow therapeutic margin/index, such as digitalis and/or anticoagulants.

Special care should be taken when administering selegiline to patients who have labile hypertension, cardiac arrhythmias, severe angina pectoris, psychosis or a history of peptic ulceration as aggravation of these conditions may occur during treatment.

Studies have related the risk of an increased hypotensive response to concomitant administration of selegiline and levodopa, in patients with cardiovascular risk.

As selegiline is a specific MAO-B inhibitor, foods containing tyramine have not been reported to induce hypertensive reactions during selegiline treatment at recommended dosage (i.e., it does not cause the so-called “cheese-effect”). Therefore, no dietary restrictions are required.

However, in case of combination of selegiline and conventional MAO inhibitors or MAO-A, dietary restrictions (i.e. avoidance of food with large amounts of tyramine such as aged cheese and yeast products) are recommended.

Selegiline is indicated for the treatment of Parkinson’s disease which, in most cases, is a disease occurring after childbearing age.

The available safety data concerning the use during pregnancy is insufficient to justify the use of selegiline in this patient group.

Studies in animals have shown reproductive toxicity only at high multiple of human doses. As a precautionary measure, it is preferable to avoid the use of selegiline in pregnancy.

Selegiline is indicated for the treatment of Parkinson’s disease which, in most cases, is a disease occurring after childbearing age.

The available safety data concerning the use during lactation is insufficient to justify the use of selegiline in this patient group.

It is unknown whether selegiline is excreted in human breast milk. The excretion of selegiline in milk has not been studied in animals. Physico-chemical data on selegiline point to excretion in breast milk and a risk to the suckling child cannot be excluded. Selegiline should not be used during breast-feeding.

Even when used correctly, this medicine may cause dizziness or can affect reaction capacity to the extent that driving or operating machinery is affected and therefore patients should be advised not to drive or use machines if they experience these adverse reactions during treatment.

This medicine can impair cognitive function and can affect a patient’s ability to drive safely. This class of medicine is in the list of drugs included in regulations under 5a of the Road Traffic Act 1988. When prescribing this medicine, patients should be told:

• The medicine is likely to affect your ability to drive.
• Do not drive until you know how the medicine affects you.
• It is an offence to drive while under the influence of this medicine.
• However, you would not be committing offence (called ‘statutory defence’) if:
  • The medicine has been prescribed to treat a medical or dental problem and
  • You have taken it according to the instructions given by the prescriber and in the information provided with the medicine and
  • It was not affecting your ability to drive safely.

The following undesirable effects have been reported with selegiline during clinical trials and/or post-marketing use. They are listed below as MedDRA preferred term by system organ class and frequency. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. Very common (≥1/10); Common (≥1/100 to <1/10); Uncommon (≥1/1,000 to <1/100); Rare (≥1/10,000 to <1/1,000); Very rare (<1/10,000), Not known (cannot be established from the available data).

Infections and infestations

Uncommon: Pharyngitis

Blood and lymphatic system disorders

Uncommon: Leucocytopenia, thrombocytopenia

Metabolism and nutrition disorders

Uncommon: Loss of appetite

Psychiatric disorders

Common: Sleeping disorders, confusion, hallucinations, depression

Uncommon: Abnormal dreams, agitation, anxiety, psychoses, mood change

Not known: Hypersexuality*

Nervous system disorders

Common: Abnormal movements (such as dyskinesias, akinesia, bradykinesia), dizziness, headache, impaired balance, tremor

Uncommon: mild transient sleep disorder

Eye disorders

Uncommon: Blurred vision

Ear and labyrinth disorders

Common: Vertigo

Cardiac disorders

Common: Bradycardia

Uncommon: Arrhythmias, palpitations, angina pectoris, supraventricular tachycardia

Vascular disorders

Common: hypotension, hypertension

Uncommon: Orthostatic hypotension

Rare: Postural hypotension

Respiratory, thoracic and mediastinal disorders

Common: Nasal congestion, sore throat

Uncommon: Dyspnoea

Gastrointestinal disorders

Very common: Stomatitis

Common: Nausea, constipation, diarrhoea, mouth ulceration

Uncommon: Dry mouth

Hepato-biliary disordrers

Uncommon: Transient rise of serum alanine aminotransferase (ALAT)

Skin and subcutaneous tissue

Common: Sweating increased

Uncommon: Hair loss, skin eruptions

Rare: Skin reactions

Muskuloskeletal and lymphatic system disorders

Common: Arthralgia, back pain, muscle cramps

Uncommon: Myopathy

Renal and urinary disorders

Uncommon: Micturition disorders

Not known: Urinary retention

General disorders and administration site conditions

Common: Fatigue

Uncommon: Chest pain, irritability, ankle oedema

Injury, poisoning and procedural complications

Common: Fall

Investigations

Common: Mild hepatic enzymes increased

* Parkinson’s disease patients treated with dopamine agonists and other dopaminergic treatments have been reported as exhibiting impulse control disorders and compulsions like pathological gambling, increased libido, hypersexuality, binge eating, shopping and different kinds of compulsive/repetitive activities (punding). These may also be possible with selegiline but very few cases have been reported to date.

As selegiline potentiates the effect of levodopa (levodopa should be usually given in association with a peripheral decarboxylase inhibitor), the side-effects of levodopa may be emphasised unless the dosage of levodopa is reduced. Selegiline combination therapy may permit further reduction of levodopa dose (even by 30%).The most common undesirable effect reported for conventional tablets is dyskinesia (4% of patients) other side effects include restlessness, hyperkinesis, abnormal movements, agitation, confusion, hallucination, postural hypotension, cardiac arrhythmias. Once the optimum levodopa dose level has been established, the side-effects produced by the combination will usually be less than those caused by the levodopa therapy on its own.